RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of isotretinoin may be an effective way to prevent lung cancer. Vitamin E may prevent the side effects of isotretinoin therapy.

PURPOSE: Randomized clinical trial to study the effectiveness of vitamin E in preventing the side effects of isotretinoin in former and current smokers who are receiving isotretinoin to prevent lung cancer.

Condition	Treatment or Intervention	Phase
Lung Cancer prevention of lung cancer	Drug: isotretinoin  Drug: vitamin E	Phase III

Further Study Details: 

OBJECTIVES: I. Determine whether the addition of alpha-tocopherol (AT; vitamin E) to isotretinoin decreases the incidence of Grade II and higher toxicity of isotretinoin when administered to former and current smokers.

II. Determine the compliance rate of isotretinoin of smoker and former smokers with or without AT over a six month period.

III. Determine the feasibility of recruiting former and current smokers with or without AT over a six month period.

IV. Determine the effect of isotretinoin administration on serum retinol and retinol-binding protein levels in these patients.

PROTOCOL OUTLINE: This is randomized, placebo controlled study. Patients are stratified by smoking status (current smoker vs former smoker) and age (less than 50 vs 50 and over).

Patients are randomized to be take alpha-tocopherol (AT) orally and isotretinoin orally daily (arm I) or isotretinoin orally plus AT placebo orally daily (arm II). Treatment in each arm continues for 6 months.

Patients are followed at 1, 3, 6, and 7 months from start of treatment.

PROJECTED ACCRUAL: There will be 300 patients (150 per arm) accrued into this study over an estimated 9 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Current smokers with 20+ packs per year history of smoking OR Former smokers who discontinued smoking 1 year prior to registration (less than 5 cigarettes in the prior year) and had a 20+ packs per year history prior to discontinuing smoking

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior isotretinoin
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: No prior warfarin or its derivatives; At least 3 months since megadose vitamin A (greater than 25,000 IU/day) or beta-carotene greater than 30 mg/day or alpha-tocopherol at least 400 IU daily; No concurrent megadose vitamin A (greater than 25,000 IU/day), beta-carotene greater than 30 mg/day, alpha-tocopherol at least 400 IU daily, or other daily supplements and tonics

--Patient Characteristics--

• Age: 18 and over
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: WBC greater than 3,000/mm3; Platelet count greater than 100,000/mm3
• Hepatic: Bilirubin less than 1.5 mg/dL; SGOT less than 40 IU/mL OR SGPT less than IU/mL
• Renal: Not specified
• Other: Fasting triglycerides less than 320 mg/dL; No prior malignancy in the past 5 years except nonmelanomous skin cancer or noninvasive cervical cancer; No history of malabsorption syndrome; Not pregnant; Effective contraception required of all fertile persons

Study chairs or principal investigators

Rodger J. Winn,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000066672; MDA-DM-97078; NCI-P98-0132
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003599
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08